One-step single heater based flow synthesis setup for synthesis of inorganic particles in near ambient conditions

ABSTRACT

A flow synthesis system (FSS) based on contamination free PTFE tubing, a pump for pumping requisite solutions and a heater for heating precipitated flow suspensions has been designed. Synthesis, using FSS, eliminates the need for secondary heat-treatments and/or long ageing times required in traditional inorganic synthesis routes. The FSS was used successfully to synthesis calcium phosphates which include phase-pure and ion substituted hydroxyapatite, respectively. Biologically beneficial magnesium, zinc, carbonate and silicon ions were successfully incorporated into hydroxyapatite.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Continuation-in-Part of U.S. patent applicationSer. No. 16/373,185, filed on Apr. 2, 2019, and claims priority from andthe benefit of Pakistan Patent Application No. 378/2018, filed on May30, 2018, which are hereby incorporated by reference for all purposes asif fully set forth herein.

BACKGROUND Field

Exemplary embodiments of the invention relate generally to a flowsynthesis system (FSS) based on contamination free PTFE tubing, a pumpfor pumping requisite solutions, and a heater for heating precipitatedflow suspensions for the synthesis of inorganic particles in nearambient conditions.

Discussion of the Background

Traditional approaches for the synthesis of bioceramics depend onmaterials which require strict parameters control or very long synthesisperiods. The majority of room temperature batch synthesis methods forbioceramics tend to be multi-step, energy intensive, or time consumingprocesses. For example, in wet chemical syntheses of hydroxyapatite(HA), a maturation step (>18 h), followed by a heat treatment of 650°C., is required. Although batch hydrothermal process facilitates asimpler, lower temperature based and relatively efficient way tosynthesize phase pure HA however, most of the time it requirestemplating agents along with long reaction time (up to 24 hours).

Current continuous production of HA is carried out at temperatures inexcess of the range of 200-400° C., which is energy intensive.Furthermore, at such high temperatures, although nucleation occurs,there is substantial growth or agglomeration of smaller nuclei to formsubstantially larger particles. Additionally, there is a disadvantage ofhaving to use high temperature continuous systems, in that they areconducted in an all metal tubing setup—due to the high reactiontemperatures. Therefore, if such a process were used to makebioceramics, they would contain substantial levels of leached metalsfrom the steel (e.g. Fe, Cr, etc.). This would mean that the bioceramicsmay not be acceptable for clinical use based on unwanted metal ionspresent. Consequently, a need arises to develop smaller nano-sizedcalcium phosphates using methods, which allow for fine control overparticle sizes, preferably under relatively mild conditions oftemperature and pressure, and with purity acceptable for use in aclinical setting such as for bone replacement. One known method of HAproduction at near ambient conditions (20-60° C.) was reported in thepatent literature that involves the mixing of reagents in multiplestages using a multiple step reactor with strong stirring.

Similarly, for oxides much work has been published on ZnO and ZnO dopedmaterials' synthesis routes and applications. However, a simple andquick route that provides access to nanosized particles with tailorableproperties is highly desirable. Phase pure and doped zinc oxides aregenerally synthesized via wet-chemical/precipitation, sol-gel methods,co-precipitation, solid-thermal methods, hydrothermal synthesis,emulsion techniques, and spray pyrolysis. Flow synthesis of ZnO is arelatively new approach. Reports in literature rely on complex andexpensive flow systems which rely on high temperature and pressure.Therefore, there is a need for a simple flow methodology whichfacilitates a one-step, rapid route to synthesis.

Therefore, attempts have been made to develop a simple, low cost, clean,synthesis technique, which could work under mild conditions and allowthe synthesis of high purity stoichiometric HA and other bioceramicmaterials in a considerably short time period with a fine andcontrollable particle size (range from 20-150 nm) and controlled surfacearea (typically range from 95-300 m²g⁻¹), depending on reactionconditions.

The above information disclosed in this Background section is only forunderstanding of the background of the inventive concepts, and,therefore, it may contain information that does not constitute priorart.

SUMMARY

Devices constructed according to exemplary implementations and methodsaccording to exemplary embodiments of the invention are capable ofsynthesis of inorganic particles in near ambient conditions.

A flow synthesis system (FSS) based on contamination free PTFE tubing, apump for pumping requisite solutions and a heater for heatingprecipitated flow suspensions has been designed. This novel design isbased on the need to develop calcium phosphate and oxide basednanoceramics with tailorable properties in a simple single stepsynthesis method. Synthesis therefore, using FSS, eliminates the needfor secondary heat-treatments and/or long ageing times required intraditional inorganic synthesis routes. The FSS was used successfully tosynthesis calcium phosphates which include phase-pure and ionsubstituted hydroxyapatite, respectively. Biologically beneficialMagnesium, Zinc, Carbonate and Silicon ions were successfullyincorporated into hydroxyapatite. The versatility of FSS to synthesiscalcium phosphates based on different precursors was also elucidated inthis work. These nanoparticles can have great range of applications foruse in replacement of hard tissues such as bone and teeth, as bone graftsubstitutes, injectable solutions, coatings on metallic implants, asfillers or additives in commercial products, such as toothpastes;materials for the controlled release of drugs, or other controlledrelease therapies; reinforcements in biomedical composites, and in boneand dental cements. The novel FSS was also used to synthesize phase-pureoxides which include ZnO and CeO₂. Doped zinc oxides were also obtainedby successfully incorporation of K, Fe, Ca, Ce & Mg ions in zinc oxidewhilst retaining the original phase (proven through extensive X-rayDiffraction Studies). These compositional directives influenceparticulate properties which include size and morphology. Promisingphotocatalysts, antibacterial agents (standalone or as reinforcements inpolymers) and semiconductors were hence synthesized based on sizeablereduction in band gaps as a result of doping. Summarily, novel FSSdeveloped herein is the first instance of its kind. Its use therefore tosynthesize materials for bone regeneration, photo catalysis,antibacterial response and semiconducting applications is carefullyelucidated.

Additional features of the inventive concepts will be set forth in thedescription which follows, and in part will be apparent from thedescription, or may be learned by practice of the inventive concepts.

In an exemplary embodiment of the invention, a system includes: a pumpwith three feeds; a stainless steel T-piece reactor; and a heater havingtubing passing through it. The pump is connected to the T-piece reactor,the T-piece reactor is connected to the tubing passing through theheater, and the feeds and the tubing are formed of contamination freepolytetrafluoroethylene (PTFE).

A first feed of the pump may send a first solution to the T-piecereactor and a second feed of the pump may send a second solution to theT-piece reactor.

The third feed of the pump may send a third solution to the T-piecereactor.

The exemplary system may be used in a method to synthesize inorganicparticles, wherein the solutions from at least two feeds of the pumpreact in the T-piece reactor to form a reaction suspension.

The reaction suspension of the T-piece reactor may pass through theheater.

The suspension may exit from the heater and be collected in a containerin a continuous manner.

The first solution and second solution may be selected for continuousflow synthesis of grafted and non-grafted inorganic nanoparticles.

The first solution and second solution may be selected for the synthesisof inorganic particles and nanoparticles.

The first solution and second solution may be selected for the synthesisof inorganic particles and nanoparticles of a single phase.

The first solution and second solution may be selected for the synthesisof inorganic particles and nanoparticles belonging to different phases.

The first solution and second solution may be selected for the synthesisof inorganic particles and nanoparticles grafted with organic groups.

The first solution and second solution may be selected for synthesisbased on variable flow rates.

The pump may maintain the same flow rate in all feeds.

The reaction times may be varied based on flow rates.

The reactions times may be increased by increasing a length of thetubing in the heater.

Different solution concentrations may be used to influence reactionyield.

A pH of the feed solutions may be varied.

A pH of all feed solutions may be varied independently.

The inorganic particles may be synthesized with varying crystallinity.

The reaction temperatures may be varied.

The reaction temperatures may be varied to influence phase purity ofproduct.

The reaction temperatures may be varied to influence crystallinity.

Grafted and non-grafted inorganic particles and nanoparticles may besynthesized in gram and kilogram level yields.

Different elements may be doped into inorganic particles andnanoparticles.

The resultant particle size may be varied.

The dopant levels into inorganic particles and nanoparticles may bevaried.

The reactions may be carried out based on a water soluble reagent.

The feeds may be in the form of suspensions.

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and explanatory and areintended to provide further explanation of the invention as claimed.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are included to provide a furtherunderstanding of the invention and are incorporated in and constitute apart of this specification, illustrate exemplary embodiments of theinvention, and together with the description serve to explain theinventive concepts.

FIG. 1 illustrates a schematic of an exemplary embodiment of a FlowSynthesis System with a three reagent Feed pumped through a peristalticpump (P) into a cross-piece reaction point (X) and then into a verticalheater (H1) prior to collection immediately after exit from (H1).

FIG. 2 shows X-ray Diffraction patterns of Sample A, Sample B, andrespective versions heat treated at 1100° C. (denoted by HT).

FIG. 3 shows SEM images of: (a) Sample A at 1000× magnification with a20 μm scale, (b) Sample A at 5000× magnification with a 5 μm scale (c)Sample B at 1000× magnification with a 20 μm scale, and (d) Sample B at5000× magnification with a 5 μm scale.

FIG. 4 shows X-ray Diffraction patterns of Samples (a) A (b) B (c) C and(d) D, and an ICDD 09-432 pattern is shown in (e).

FIG. 5 shows X-ray Diffraction Patterns of (a) Sample A and (b) areference pattern of HA (ICDD Pattern #09-432).

FIG. 6 shows SEM images of samples (a) Zn-HA at 5000× magnification witha 5 μm scale, and (b) Zn-HA at 10000× magnification with a 2 μm scale,

FIG. 7 shows X-ray Diffraction Patterns of (a) Sample B and (b) areference pattern of HA (ICDD Pattern #09-432).

FIG. 8 shows SEM images of samples (a) Mg-HA at 5000× magnification witha 5 μm scale, and (b) Mg-HA at 10000× magnification with a 2 μm scale.

FIG. 9 shows X-ray Diffraction Patterns of (a) Sample C and (b) areference pattern of HA (ICDD Pattern #09-432).

FIG. 10 shows SEM images of samples (a) Si-HA at 5000× magnificationwith a 5 μm scale, and (b) Si-HA at 10000× magnification with a 2 μmscale.

FIG. 11 shows X-ray Diffraction Patterns of (a) Sample D and (b) areference pattern of HA (ICDD Pattern #09-432).

FIG. 12 shows SEM images of samples (a) Carbonated HA at 5000×magnification with a 2 μm scale, and (b) Carbonated HA at 10000×magnification with a 1 μm scale.

FIG. 13 shows X-ray Diffraction patterns of Samples (a) A (b) B (c) Cand (d) D, and an ICDD 010-0333 pattern is shown in (e).

FIG. 14 shows electron microscopy images of (a) Sample (A) 500×magnification with a 50 μm scale, (b) Sample (B) 500× magnification witha 50 μm scale, (c) Sample (C) 500× magnification with a 50 μm scale, and(d) Sample (D) 500× magnification with a 50 μm scale.

FIG. 15 shows X-ray Diffraction Patterns of Samples (a) synthesized zincoxide and (b) ICDD Pattern #36-1451.

FIG. 16 shows SEM images of samples (a) ZnO at 5000× magnification witha 5 μm scale, and (b) ZnO at 10000× magnification with a 2 μm scale.

FIG. 17 shows X-Ray Diffraction Patterns of (a) 0.5Ce—ZnO, (b) 1Ce—ZnOand (c) 2Ce—ZnO, (d) ZnO, and (e) ICDD Pattern #36-1451.

FIG. 18 shows X-Ray Diffraction Patterns of (a) 0.5Ca—ZnO, (b) 1Ca—ZnO,(c) 2Ca—ZnO, (d) ZnO, and (e) ICDD Pattern #36-1451.

FIG. 19 shows X-Ray Diffraction Patterns of (a) 0.5K—ZnO, (b) 1K—ZnO,(c) 2K—ZnO, (d) ZnO, and (e) ICDD Pattern #36-1451.

FIG. 20 shows X-Ray Diffraction Patterns of (a) 0.5Fe—ZnO, (b) 1Fe—ZnO,(c) 2Fe—ZnO, (d) ZnO, and (e) ICDD Pattern #36-1451.

FIG. 21 shows X-Ray Diffraction Patterns of (a) 0.5Mg—ZnO, (b) 1Mg—ZnO,(c) 2Mg—ZnO, (d) ZnO, and (e) ICDD Pattern #36-1451.

FIG. 22 shows SEM images of Ce—ZnO samples (a) 0.5 Ce—ZnO at 20000×magnification with a 2 μm scale, (b) 0.5 Ce—ZnO at 100000× magnificationwith a 200 nm scale, (c) 1 Ce—ZnO at a 20000× magnification with a 2 μmscale, (d) 1 Ce—ZnO at a 100000× magnification with a 200 nm, scale, (e)2 Ce—ZnO at a 20000× magnification with a 2 μm scale, and (f) 2 Ce—ZnOat 100000× magnification with a 200 nm scale.

FIG. 23 shows SEM images of K—ZnO samples (a) 0.5 K—ZnO at 20000×magnification with a 2 μm scale, (b) 0.5 K—ZnO at 100000× magnificationwith a 200 nm scale, (c) 1 K—ZnO at 20000× magnification with a 2 μmscale, (d) 1 K—ZnO at 100000× magnification with a 200 nm scale, (e) 2K—ZnO at 20000× magnification with a 2 μm scale, (f) 2 K—ZnO at 100000×magnification with a 200 nm scale.

FIG. 24 shows SEM images of Ca—ZnO samples (a) 0.5 Ca—ZnO at 20000×magnification with a 2 μm scale, (b) 0.5 Ca—ZnO at 100000× magnificationwith a 200 nm scale, (c) 1 Ca—ZnO at 20000× magnification with a 2 μmscale, (d) 1 Ca—ZnO at 100000× magnification with a 200 nm scale, (e) 2Ca—ZnO at 20000× magnification with a 2 μm scale, (f) 2 Ca—ZnO at100000× magnification with a 200 nm scale.

FIG. 25 shows SEM images of Fe—ZnO samples (a) 0.5Fe—ZnO at 20000×magnification with a 2 μm scale, (b) 0.5Fe—ZnO at 100000× magnificationwith a 200 nm scale, (c) 1Fe—ZnO at 20000× magnification with a 2 μmscale, (d) 1Fe—ZnO at 100000× magnification with a 200 nm scale, (e)2Fe—ZnO at 10000× magnification with a 2 μm scale, (f) 2Fe—ZnO at100000× magnification with a 200 nm scale.

FIG. 26 shows SEM images of Mg—ZnO samples (a) 0.5 Mg—ZnO at 20000×magnification with a 2 μm scale, (b) 0.5Mg—ZnO at 100000× magnificationwith a 200 nm scale, (c) 1Mg—ZnO at 20000× magnification with a 2 μmscale, (d) 1Mg—ZnO at 100000× magnification with a 200 nm scale, (e)2Mg—ZnO at 20000× magnification with a 2 μm scale, (f) 2Mg—ZnO at100000× magnification with a 200 nm scale.

FIG. 27 shows X-Ray Diffraction Patterns of (a) CeO2, and (b) ICDDPattern #34-0394.

FIG. 28 shows SEM images of samples (a) CeO2 at 5000× magnification witha 5 μm scale, and (b) at 10000× magnification with a 10 μm scale.

FIG. 29 shows FTIR spectra of Pure ZnO and Grafted ZnO.

DETAILED DESCRIPTION

In the following description, for the purposes of explanation, numerousspecific details are set forth in order to provide a thoroughunderstanding of various exemplary embodiments or implementations of theinvention. As used herein “embodiments” and “implementations” areinterchangeable words that are non-limiting examples of devices ormethods employing one or more of the inventive concepts disclosedherein. It is apparent, however, that various exemplary embodiments maybe practiced without these specific details or with one or moreequivalent arrangements. In other instances, well-known structures anddevices are shown in block diagram form in order to avoid unnecessarilyobscuring various exemplary embodiments. Further, various exemplaryembodiments may be different, but do not have to be exclusive. Forexample, specific shapes, configurations, and characteristics of anexemplary embodiment may be used or implemented in another exemplaryembodiment without departing from the inventive concepts.

Unless otherwise specified, the illustrated exemplary embodiments are tobe understood as providing exemplary features of varying detail of someways in which the inventive concepts may be implemented in practice.Therefore, unless otherwise specified, the features, components,modules, layers, films, panels, regions, and/or aspects, etc.(hereinafter individually or collectively referred to as “elements”), ofthe various embodiments may be otherwise combined, separated,interchanged, and/or rearranged without departing from the inventiveconcepts.

When an element is referred to as being “on,” “connected to,” or“coupled to” another element, it may be directly on, connected to, orcoupled to the other element or intervening elements may be present.When, however, an element is referred to as being “directly on,”“directly connected to,” or “directly coupled to” another element, thereare no intervening elements present. To this end, the term “connected”may refer to physical, electrical, and/or fluid connection, with orwithout intervening elements. Further, the D1-axis, the D2-axis, and theD3-axis are not limited to three axes of a rectangular coordinatesystem, such as the x, y, and z-axes, and may be interpreted in abroader sense. For example, the D1-axis, the D2-axis, and the D3-axismay be perpendicular to one another, or may represent differentdirections that are not perpendicular to one another. For the purposesof this disclosure, “at least one of X, Y, and Z” and “at least oneselected from the group consisting of X, Y, and Z” may be construed as Xonly, Y only, Z only, or any combination of two or more of X, Y, and Z,such as, for instance, XYZ, XYY, YZ, and ZZ. As used herein, the term“and/or” includes any and all combinations of one or more of theassociated listed items.

Although the terms “first,” “second,” etc. may be used herein todescribe various types of elements, these elements should not be limitedby these terms. These terms are used to distinguish one element fromanother element. Thus, a first element discussed below could be termed asecond element without departing from the teachings of the disclosure.

Spatially relative terms, such as “beneath,” “below,” “under,” “lower,”“above,” “upper,” “over,” “higher,” “side” (e.g., as in “sidewall”), andthe like, may be used herein for descriptive purposes, and, thereby, todescribe one elements relationship to another element(s) as illustratedin the drawings. Spatially relative terms are intended to encompassdifferent orientations of an apparatus in use, operation, and/ormanufacture in addition to the orientation depicted in the drawings. Forexample, if the apparatus in the drawings is turned over, elementsdescribed as “below” or “beneath” other elements or features would thenbe oriented “above” the other elements or features. Thus, the exemplaryterm “below” can encompass both an orientation of above and below.Furthermore, the apparatus may be otherwise oriented (e.g., rotated 90degrees or at other orientations), and, as such, the spatially relativedescriptors used herein interpreted accordingly.

The terminology used herein is for the purpose of describing particularembodiments and is not intended to be limiting. As used herein, thesingular forms, “a,” “an,” and “the” are intended to include the pluralforms as well, unless the context clearly indicates otherwise. Moreover,the terms “comprises,” “comprising,” “includes,” and/or “including,”when used in this specification, specify the presence of statedfeatures, integers, steps, operations, elements, components, and/orgroups thereof, but do not preclude the presence or addition of one ormore other features, integers, steps, operations, elements, components,and/or groups thereof. It is also noted that, as used herein, the terms“substantially,” “about,” and other similar terms, are used as terms ofapproximation and not as terms of degree, and, as such, are utilized toaccount for inherent deviations in measured, calculated, and/or providedvalues that would be recognized by one of ordinary skill in the art.

Unless otherwise defined, all terms (including technical and scientificterms) used herein have the same meaning as commonly understood by oneof ordinary skill in the art to which this disclosure is a part. Terms,such as those defined in commonly used dictionaries, should beinterpreted as having a meaning that is consistent with their meaning inthe context of the relevant art and should not be interpreted in anidealized or overly formal sense, unless expressly so defined herein.

As illustrated in FIG. 1, the Flow Synthesis System consists of singleperistaltic pump P with multiple inputs and outputs, connected to6-meter-long Polytetrafluoroethylene PTFE tubing (which gives goodresistance to strong pH and is easy to clean). Reagents were stored in areservoir of required size which was connected to the pump using ¼ inchexternal diameter PTFE tubing. The tubing exiting from the pump wasconnected to a 1/16 inch stainless steel 316 L grade (SS316L) T-piecewhen two reagent inputs were used or to a 1/16 inch SS316LCross(X)-piece when 3 reagent inputs were used. The T-piece and theX-piece act as reaction points in the FSS. After the mixing point, thePTFE tube was coiled inside a vertical furnace (1000 W) where length of750 Watts programmable furnace was 0.4 meters and diameter was 0.3meters. The total length of tubing from the pump to collection was 6.0meters. Solutions (reagent feeds) were prepared in glass beakers,respectively, followed by continuous stirring of solutions on a magneticstirrer plate. The precursor solutions were pumped at a specific flowrate (depend on conditions of reactions) to meet at the 1/16-inch SS316LT-piece. This initial mixture was connected to 6-meter long ¼-inchexternal diameter PTFE tubing which was coiled inside a verticallyaligned heater. The product is collected from the end of the tube atambient pressure. In typical reaction reagents all flow through the pumpto react at the T or X piece resulting in immediate precipitation—thissuspension then flows into the hot zone H1 regulated at the requiredtemperature. The particles in the suspension react to the temperature inthe hot zone and exit at an elevated temperature. Suspensions arecollected in a beaker and can be oven and freeze dried to obtain nanoand micro sized particles.

Calcium hydroxide solution and Diammonium hydrogen phosphate with theconcentrations shown in Table 1 were pumped using a peristaltic pump ata flow rate of 30 ml/min with the exit temperature at 70° C. (controlledusing adjusting set temperature of Heater H1). Resulting suspension wascollected immediately after exit. The suspension was then centrifugedfollowed by washing (×2 times) using deionized water. Synthesizedsamples were then freeze dried using an Alpha 1-2 LD plus freeze dryer.

TABLE 1 Concentrations and volumes of precursors used for synthesis of 2samples of hydroxyapatite (A, B) in this study. Volume Volume ReactionsConcentration (mL) Concentration (mL) ID Diammonium hydrogen phosphateCalcium Hydroxide Sample A 0.3M 250 0.5M 250 Sample B 0.3M 250 0.3M 250

X-ray Diffraction: XRD analysis confirmed samples to be phase purehydroxyapatite when compared to ICDD Pattern #09-432 as no other peakwas observed in the spectrum (please see FIG. 2).

Scanning Electron Microscopy: SEM was performed to analyze morphologyand particle size of the samples synthesized. The average particle sizewas calculated at 1000× and 5000× magnifications about 4 μm as seen inimage (a) of FIG. 3. Agglomerates of particles can be seen in images(a), (b), (c), and (d) of FIG. 3.

Synthesis of Hydroxyapatite Using Calcium Nitrate Tetrahydrate &Diammonium Hydrogen Phosphate

Phase pure HA: Similarly, reactions were carried out with Diammoniumhydrogen phosphate solution and Calcium nitrate tetrahydrate solutionwith the different concentrations as shown in Table 2 were pumped at aflow rate 30 ml/min with the exit temperature 70° C. The pH wasmaintained 10 with 3 ml of ammonium hydroxide solution. Then the mixturewas centrifuged and filtered and washed twice by de-ionized water.

TABLE 2 Concentrations and volumes of precursors used for synthesis of 4samples of hydroxyapatite (A, B, C and D) in this study. Volume VolumeConcentration (mL) Concentration (mL) Reactions Diammonium Calciumnitrate ID hydrogen phosphate tetra hydrate Sample A 0.3M 200 0.5M 200Sample B 0.3M 200 0.6M 200 Sample C 0.3M 200 0.3M 200 Sample D 0.3M 2000.6M 200

X-ray Diffraction: confirms the synthesis of Hydroxyapatite whencompared to ICDD Pattern #09-432. But another peak was observed in thespectrum near 30 Theta, which was possibly due to unreacted CalciumHydroxide, as shown in images (a)-(e) of FIG. 4.

Ion Substituted Hydroxyapatite: Substituted reactions were carried outwith Diammonium hydrogen phosphate solution and Calcium nitratetetrahydrate solution with the different concentrations as shown inTable 3 were pumped at a flow rate 30 ml/min with the exit temperature70° C. The pH was maintained 10 with 3 ml of ammonium hydroxidesolution. Then the mixture was centrifuged and filtered and washed twiceby de-ionized water.

TABLE 3 Concentrations and volumes of precursors used for synthesis of 4samples of Substituted hydroxyapatite (A, B, C and D) in this study.Volume Volume Reactions ID Concentration (mL) Concentration (mL) SampleA Zinc Substituted HA 0.15M 200 0.3M 200 Sample B Magnesium substitutedHA 0.15M 200 0.3M 200 Sample C Silicone Substituted HA 0.15M 200 0.3M200 Sample D Carbonated HA 0.15M 200 0.3M 200

Zinc Substituted Hydroxyapatite (Zn-HA)

X-ray Diffraction: It is clearly seen from XRD pattern (a) of FIG. 5that all peaks match to those of HA (compared to ICDD Pattern #09-432),which confirms the phase purity.

Scanning Electron Microscopy: SEM was performed to analyze morphologyand particle size of the samples synthesized in this study. Images (a)and (b) of FIG. 6 show rod like morphology of Zn-HA. Average size of therods observed was measured to be 10 um (±3) in length×2 um (±0.7) in dia(25 particles measured).

Magnesium Substituted Hydroxyapatite (Mg-HA)

X-ray Diffraction: It is clearly seen from the XRD pattern (a) of FIG. 7that all peaks match those of HA when compared to ICDD Pattern #09-432.This confirms the phase purity.

Scanning Electron Microscopy: Scanning Electron Microscopy was performedfor morphological analysis of Mg-HA in this study. Images (a) and (b) ofFIG. 8 reveal rod like structure of the synthesized samples. Averagesize of the rods observed was measured to be 15 um (±2) in length x 0.63um (±0.2) in dia (25 particles measured).

Silicone Substituted Hydroxyapatite (Si-HA)

X-Ray Diffraction: The XRD pattern (a) in FIG. 9 gave a good match toICDD pattern 09-432, indicating a good match to phase purehydroxyapatite.

Scanning Electron Microscopy: images (a) and (b) of FIG. 10 show the SEMimages of Si-HA. Average size of the rods observed was measured to be 8um (±2) in length x 0.8 um (±0.3) in dia (25 particles measured).

Carbonate Substituted Hydroxyapatite (CO₃-HA)

X-Ray Diffraction: The XRD pattern (a) of CO₃-HA (Sample D) in FIG. 11showed a good match to phase pure HA (ICDD Pattern 09-432).

Scanning Electron Microscopy: images (a) and (b) of FIG. 12 show SEMimages of CO₃-HA (Sample D) synthesized using the flow synthesis system.The samples revealed to be irregular shaped particles. Average particlesize was observed to be 0.7 μm (25 particles measured).

Synthesis of Zinc Phosphates

For the synthesis of zinc phosphates, stock solutions of 0.15M zincnitrate and 0.1M di ammonium hydrogen phosphase were prepared indeionized water respectively. For first reaction (Sample A), 250 ml eachsolution was used and pumped at a flow rate of 30 ml/min. In thisreaction no pH was adjusted and no heating was involved.

In a second reaction (Sample B) 250 ml of each solution were pumped atsame flow rate but pH was adjusted by adding 3 ml of ammonia solution inthe original reagent solutions. The third reaction (Sample C) was againdone at same flow rate but no pH adjusted but heating was involved up to70° C. In the fourth reaction (Sample D), again we used 250 ml of eachsolution but in this reaction no heating and pH adjustment were involvedas shown in Table 4. After collection the suspensions were filteredfollowed by washing with deionized water (×2 times). All the sampleswere dried in drying oven at 80° C. for 24 hours.

Table: 4 shows the reactions IDs, reaction parameters, concentrationsand volumes of precursors used for synthesis of zinc phosphates in thisembodiment.

Volume Volume Reactions Concentration (mL) Concentration (mL) IDParameters Diammonium Hydroxide Zinc Nitrate tetra hydrate Sample A NoHeating, No pH 0.1M 250 0.15M 250 Sample B Heating, pH adjusted 0.1M 2500.15M 250 Sample C Heating, No pH 0.1M 250 0.15M 250 Sample D NoHeating, pH adjusted 0.1M 250 0.15M 250

X-ray Diffraction: When no heating was used without any pH adjustmentZn₃ (PO₄)₂.2H₂O phase was observed for Sample A in pattern (a) of FIG.13. Application of heat and pH adjustment led to phase zinc phosphate asseen in pattern (b) FIG. 13. Using heat alone (i.e. without pHadjustment) zinc phosphate tetra hydrate (hopite) was observed inpattern (c) FIG. 13 for Sample C. With pH adjustment alone (i.e. noheating) zinc phosphate hydrate (ICDD Pattern #010-0333) was observed asseen in pattern (d) FIG. 13 for Sample D.

Scanning Electron Microscopy: SEM analysis reveals image (a) of FIG. 14to have a plate like morphology with an average plate size of 12 μm by22 μm but when the pH parameter is involved, the size of the plateletsbecome bigger as shown in image (b) of FIG. 14, being 34 μm by 69 μm andwhen only heating is involved the platelets are aggregated in a peculiarway to form clusters of large platelets as shown in image (c) of FIG.14. In image (d) of FIG. 14, the platelets fuse into each other withplate size 13 μm by 18 μm due to heating and pH parameters.

Synthesis of Phase Pure and Ion Substituted Oxides

Phase Pure Zinc Oxide

Zinc oxide was synthesized using the 0.3M Zn(NO₃)₂.6H₂O and 0.6M NaOHsolutions with a flow rate of 30 ml/min with exit temperature of 70° C.The synthesized samples were then freeze dried for 24 hours to obtainphase pure ZnO.

X-ray Diffraction: pattern (a) of FIG. 15 reveals phase pure ZnO wassynthesized when compared to ICDD Pattern #36-1451. No other phases wereobserved.

Scanning Electron Microscopy: images (a) and (b) of FIG. 16 revealparticle size ranging from 200-400 nm of spherical shape for phase pureZnO synthesized using the flow synthesis system.

Ion Doped Zinc Oxides

To synthesize doped-Zinc oxides, pre-weighed dopant sources[Ce(NO₃)₃.6H₂O, KNO₃, Ca(NO₃)₂.4H₂O, Mg(NO₃)₂.6H₂O, & Fe(NO₃)₃.9H₂O]were added to Zinc Nitrate solution.

Cerium, Potassium, Magnesium, Calcium and Iron ions were doped in ZincOxide in varying (theoretical) concentrations (0.5 mole %, 1 mole % & 2mole %). Please see Table 5 for details.

Table: 5 shows the amounts of dopant ion sources added to Zinc Nitrateprecursor solution.

Element 0.5 mole % 1 mole % 2 mole % Cerium (CeNO₃•6H₂O) 0.1620 g 0.3250g 0.6510 g Potassium (KNO₃) 0.0379 g 0.0700 g 0.1500 g Calcium(Ca(NO₃)₂•4H₂O) 0.0886 g 0.1170 g 0.3540 g Iron (Fe(NO₃)₃•9H₂O) 0.1500 g0.3000 g 0.6060 g Magnesium (Mg(NO₃)₂•6H₂O) 0.0960 g 0.1900 g 0.3800 g

Elemental Analysis (using SEM-EDS): An EDS detector attached to the SEMwas used to verify the dopant ions presence in synthesized oxides. Thespectra revealed no additional impurities. The results are summarized inTable 6 below. It was observed that the measured dopant amount wasgenerally lesser than the added dopant amount. This difference may beattributed to the high diffusivity of the flow process which providesless (hence quick) residence times. These results elucidate thatsuccessful doping was achieved.

TABLE 6 Dopant amounts (mole %) added to precursor solution(theoretical) and the measured dopants amounts (mole %) Mole % AverageWeight % Element (Theoretical) (Evaluated) Cerium 0.50 0.45 1.00 2.102.00 2.64 Potassium 0.50 0.03 1.00 0.05 2.00 0.12 Calcium 0.50 0.01 1.000.04 2.00 0.09 Iron 0.50 0.40 1.00 0.64 2.00 1.41 Magnesium 0.50 0.331.00 0.36 2.00 0.57

X-Ray Diffraction: patterns (a)-(d) of FIG. 17 show the XRD pattern ofcerium doped Zinc Oxides. The XRD patterns gave a good match to ICDDPattern #36-1451, revealing them to be all Zinc Oxides. With an increasein cerium content from 0.5-2.0 wt % (theoretical) the peaks shifted.This is possibly due to incorporation of the cerium ion in ZnO matrixand resulted effect on lattice. Moreover, peak broadening wasnoticeable, due to small particle sizes. This may also be due to lessercrystallinity due to low temperature synthesis. Similar trends wereobserved for Ca, K, Fe and Mg doping, as shown in FIGS. 18-21.

Furthermore, it was observed that the sharpness of the peak reducesalong with shift as the dopant concentration increases. It can beinferred that the dopant affects decreases the crystallinity due to ZnOlattice distortion.

Coupled with the confirmation of doping from EDS elemental analysis, theshift in peaks confirms the incorporation of dopant ions in the ZnOlattice. In all the cases, the observed samples were found to bephase-pure (i.e. no other oxides were detected). It is evident that thedopants have broadened the spectra which depicts change in particlesize; which were then validated by SEM results.

Scanning Electron Microscopy: Scanning Electron Microscopy was used toinvestigate the effect of dopant concentrations on particle morphologyand aggregation.

Images (a) and (b) of FIG. 22 show rounded morphology and independentparticles of 0.5 mole % (theoretical) CeZnO nanoparticles at 20 k×Magnification. The size of nanoparticles was recorded at 20 k×magnification, the nanoparticles range from 66.1 nm to 271.1 nm and theaverage size recorded was 177.7558 nm. As the Cerium percent wasincreased to 1 mole %, the independent particles were reduced andnanoparticles were fused together and average size recorded was 585.0361nm, as shown in images (c) and (d) of FIG. 22. The size of the particleswas also increased with the increase in cerium percentage. Size rangerecorded was between 53.359 nm to 2523.239 nm, as shown in images (e)and (f) of FIG. 22. Further increase in Cerium percentage, the particlesattained more uniform fused morphology (Range: 189 nm to 1509.484 nm)and average size recorded was 610 nm per image (e) of FIG. 22.

At lower concentration of potassium i.e. 0.5 mole %, the nanoparticleswere clustered together and formed agglomerates, the high magnificationimages (a) and (b) of FIG. 23 verify the particle fusion. The averageparticle size recorded was 224 nm and depicts the irregular morphology,as shown in images (a) and (b) of FIG. 23. As the potassiumconcentration was increased to 1 mole %, the morphology became moreuniform and particles were arranged in a 4-petal arrangement fusedtogether to form bigger particle (˜447.155 nm) in a regular manner, asshown in images (c) and (d) of FIG. 23. However, at 2 mole % potassium,the morphology became more regular fused four petal arrangements. Noindependent particles were seen and average size recorded was 550.7154nm, as shown in images (e) and (f) of FIG. 23.

The calcium doping at 0.5 mole % resulted in agglomeration ofnanoparticles. The image (a) at low magnification of FIG. 24demonstrates the irregular arrangement of particles which are fusedtogether. The average size recorded was 112 nm, as shown in images (a)and (b) of FIG. 24. With increase in Calcium percentage (1 mole %) themorphology attained a certain pattern which was uniform than theprevious one and particles size was increased as well, as shown in image(c) of FIG. 24. With further increase, the pattern became more regular,the independent particles were reduced to almost zero. Image (f) of FIG.24 shows the fusion of globules in a specific manner hence attaining aregular pattern, as shown in image (e) of FIG. 24.

0.5 mole % Fe doped ZnO depicted very small independent features ofabout 33.194 nm to 126.399 nm at low magnification. However, at highmagnification the fused entities were spotted (˜72.05812 nm), as shownin images (a) and (b) of FIG. 25. As the Fe percentage was increased thefeatures became larger. In fact, a combination was large and smallfeatures were seen agglomerated together, as shown in images (c) and (d)of FIG. 25. At further increase the particles became larger andglobular, but highly fused together, as shown in images (e) and (f) ofFIG. 25.

Similarly, the doping of Mg to ZnO lead to particle growth when thedopant concentration was increased to 2%, as shown in images (e) and (f)of FIG. 26. At 0.5% Mg concentration, the particles' size was smallerand rounded structure which was independent, as shown in images (a) and(b) of FIG. 26. However, with the increase in dopant amount the size wasincreased along with particle fusion, as shown in images (c) and (d) ofFIG. 26.

Phase Pure Cerium Oxide Synthesis

Cerium oxide was synthesized using the reagents cerium nitrate tetrahydrate (0.1M in 250 ml water) and sodium hydroxide (1M in 250 ml water)at a flow rate of 30 ml/min. The synthesized sample was freeze dried at4000 rpm followed by twice washing.

X-Ray Diffraction: XRD pattern shown in FIG. 27 corresponds to phasepure CeO₂ as compared to ICDD pattern #34-0394. No secondary phase wasobserved in the synthesized sample.

Scanning Electron Microscopy: Scanning Electron Microscopy of CeO₂ wasperformed to analyze particle size and morphology. FIG. 28(a)-(b) showsparticle size ranging from 2 μm-10 μm (25 particles measured).

Grafted Oxides

Surface modification using the flow synthesis system was carried out. Amonomer urethane dimethacrylate (UDMA) was grafted onto ZnO particles byutilizing a third stream in the pumps.

FIG. 29 shows the FTIR image of phase pure and grafted ZnO. The broadband at 3350-3500 cm⁻¹ is due to stretching vibrations of OH group onsurface of ZnO particles seen in both FTIR spectra. The sharp peak at1550 cm⁻¹ in FTIR spectrum for grafted ZnO is attributed to C—O, thesecond amide peak. This peak is absent in the non-grafted ZnO. Thisproves that UDMA was successfully grafted onto ZnO. The sharp peak at1350 cm⁻¹ is carbonate peak which changes after grafting of polymer. Thepeak observed at 830 cm⁻¹ is due to zinc.

Although certain exemplary embodiments and implementations have beendescribed herein, other embodiments and modifications will be apparentfrom this description. Accordingly, the inventive concepts are notlimited to such embodiments, but rather to the broader scope of theappended claims and various obvious modifications and equivalentarrangements as would be apparent to a person of ordinary skill in theart.

1. A system comprising: a pump with three feeds; a stainless steelT-piece reactor; and a heater having tubing passing through it, wherein:the pump is connected to the T-piece reactor, the T-piece reactor isconnected to the tubing passing through the heater, and the feeds andthe tubing are formed of contamination free polytetrafluoroethylene(PTFE).
 2. The system of claim 1, wherein a first feed of the pump sendsa first solution to the T-piece reactor and a second feed of the pumpsends a second solution to the T-piece reactor.
 3. The system of claim2, wherein the third feed of the pump sends a third solution to theT-piece reactor.
 4. A method to synthesize at least one of inorganicparticles and inorganic nanoparticles, comprising: providing a systemcomprising: a peristaltic pump with three feeds configured for 30 ml/minflow rates; a stainless steel T-piece or X-piece reactor; and a heaterhaving tubing passing through it, wherein: the pump is connected to theT-piece or X-piece reactor, the T-piece or X-piece reactor is connectedto the tubing passing through the heater, and the feeds and the tubingare formed of contamination free polytetrafluoroethylene (PTFE); sendinga first solution with a first feed of the pump at a flow rate of 30ml/min to the T-piece or X-piece reactor; sending a second solution witha second feed of the pump at a flow rate of 30 ml/min to the T-piece orX-piece reactor; and reacting the solutions in the T-piece or X-piecereactor to form a reaction suspension.
 5. The method of claim 4, furthercomprising passing the reaction suspension of the T-piece or X-piecereactor passes through the heater.
 6. The method of claim 5, furthercomprising discharging the suspension from the heater and is collectedcollecting the suspension in a container in a continuous manner.
 7. Themethod of claim 4, further comprising selecting the first solution andsecond solution for continuous flow synthesis of grafted and non-graftedinorganic nanoparticles.
 8. The method of claim 4, further comprisingselecting the first solution and second solution for the synthesis ofinorganic particles and nanoparticles.
 9. The method of claim 4, furthercomprising selecting the first solution and second solution for thesynthesis of inorganic particles and nanoparticles of a single phase.10. The method of claim 4, further comprising selecting the firstsolution and second solution for the synthesis of inorganic particlesand nanoparticles belonging to different phases.
 11. The method of claim4, further comprising selecting the first solution and second solutionfor the synthesis of inorganic particles and nanoparticles grafted withorganic groups.
 12. The method of claim 4, further comprising selectingthe first solution and second solution for synthesis based on variableflow rates.
 13. The method of claim 4, further comprising maintaining asame flow rate in all feeds.
 14. (canceled)
 15. The method of claim 4,further comprising increasing reaction times by increasing a length ofthe tubing in the heater.
 16. The method of claim 4, further comprisingusing different solution concentrations to influence reaction yield. 17.The method of claim 4, further comprising varying a pH of the feedsolutions.
 18. The method of claim 4, further comprising independentlyvarying a pH of all feed solutions.
 19. The method of claim 4, furthercomprising synthesizing inorganic particles with varying crystallinity.20. The method of claim 4, further comprising varying reactiontemperatures.
 21. The method of claim 4, further comprising varyingreaction temperatures to influence phase purity of product.
 22. Themethod of claim 4, further comprising varying reaction temperatures toinfluence crystallinity.
 23. The method of claim 4, further comprisingsynthesizing grafted and non-grafted inorganic particles andnanoparticles in gram or kilogram level yields.
 24. The method of claim4, further comprising doping different elements into inorganic particlesand nanoparticles.
 25. The method of claim 4, further comprising varyingresultant particle size is varied.
 26. The method of claim 4, furthercomprising varying dopant levels into inorganic particles andnanoparticles.
 27. The method of claim 4, further comprising carryingout reactions based on a water soluble reagent.
 28. The method of claim4, further comprising providing the feeds in the form of suspensions.